Proteomic analysis reveals plasma haptoglobin, interferon-γ, and interleukin-1β as potential biomarkers of pediatric refractory epilepsy.

Autor: Saengow VE; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Chiangjong W; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Khongkhatithum C; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Changtong C; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Chokchaichamnankit D; Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand., Weeraphan C; Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand., Kaewboonruang P; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Thampratankul L; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Manuyakorn W; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Hongeng S; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Srisomsap C; Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand., Svasti J; Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand; Applied Biological Sciences Program, Chulabhorn Graduate Institute, Bangkok, Thailand., Chutipongtanate S; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Electronic address: schuti.rama@gmail.com., Visudtibhan A; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Electronic address: anannit.vis@mahidol.ac.th.
Jazyk: angličtina
Zdroj: Brain & development [Brain Dev] 2021 Mar; Vol. 43 (3), pp. 431-439. Date of Electronic Publication: 2020 Nov 30.
DOI: 10.1016/j.braindev.2020.11.001
Abstrakt: Background: Children with refractory epilepsy (RE) are associated with increased mortality rate, nonfatal injuries, disability, and diminished quality of life. Biomarkers for the early prediction of RE is still an unmet need.
Methods: Eighteen children with RE and six age-matched unrelated controls were included in this study. Plasma samples were prefractionated by the optimized thermal treatment before proteomic analysis using 2DE-LC-MS/MS. Bioinformatic analysis was carried out using STRING protein network. Immunoassay of unprocessed plasma was applied to confirm changes of proteins of interest. P-value < 0.05 was considered statistically significant.
Results: Proteomic analysis (n = 6 each group) revealed nine differentially expressed proteins, i.e., haptoglobin, S100A9, serpin B1, apolipoprotein A-I, apolipoprotein A-IV, apolipoprotein C-II, alpha-1-acid glycoprotein 1 and 2, and transthyretin. Western immunoblotting confirmed haptoglobin upregulation in the RE group. STRING protein network predicted the inflammatory cytokines, i.e., interferon gamma (IFN-γ), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), play roles in pathophysiology in RE patients. Cytokine immunoassay (n = 24, 18 RE vs. 6 controls) exhibited plasma IFN-γ was upregulated in RE patients as compared to the healthy individuals (median [IQR]; 2.9 [2.9, 4.9] vs. 1.32 [0.8, 1.5] pg/mL, p = 0.0013), and plasma IL-1β was significantly downregulated in patients (1.0 [0.2, 1.9] vs. 4.5 [1.9, 11.0] pg/mL, p = 0.01). TNF-α had no difference between groups. The results suggest that haptoglobin may be associated with oxidative brain damage, while IFN-γ and IL-1β may be involved with neuroinflammation.
Conclusions: Alterations in plasma haptoglobin, IFN-γ, and IL-1β were associated with RE patients. Future studies using a combination of these candidate biomarkers may help predict the intractability of epilepsy in pediatric populations.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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